CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress

Abstract

Early on, corticotropin-releasing factor (CRF), a hallmark brain peptide mediating many components of the stress response, was shown to affect food intake inducing a robust anorexigenic response when injected into the rodent brain. Subsequently, other members of the CRF signaling family have been identified, namely urocortin (Ucn) 1, Ucn 2, and Ucn 3 which were also shown to decrease food intake upon central or peripheral injection. However, the kinetics of feeding suppression was different with an early decrease following intracerebroventricular injection of CRF and a delayed action of Ucns contrasting with the early onset after systemic injection. CRF and Ucns bind to two distinct G-protein coupled membrane receptors, the CRF1 and CRF2. New pharmacological tools such as highly selective peptide CRF1 or CRF2 agonists or antagonists along with genetic knock-in or knock-out models have allowed delineating the primary role of CRF2 involved in the anorexic response to exogenous administration of CRF and Ucns. Several stressors trigger behavioral changes including suppression of feeding behavior which are mediated by brain CRF receptor activation. The present review will highlight the state-of-knowledge on the effects and mechanisms of action of CRF/Ucns-CRF1/2 signaling under basal conditions and the role in the alterations of food intake in response to stress.

A comparison between the equine and bovine hypothalamus-pituitary-adrenocortical axis

“…Corticotropin-releasing factor and urocortins bind to 2 distinct G-protein-coupled membrane receptors, CRF1 and CRF2 [18,26,27]. The biological effects of these peptides are mediated and modulated not only by CRF receptors but also via a highly conserved CRFbinding protein [25].…”

Testing hypotheses about individual variation in plasma corticosterone in free-living salamanders

“…A review of GC concentrations in freeliving vertebrates found that many species of amphibians, reptiles and birds seasonally modulate GC release, with both baseline and stress-induced levels being highest during times of breeding (Romero, 2002). Although far less studied than GCs in terms of patterns of variation, levels of CRH peptide are also variable (Crespi and Denver, 2005;Denver, 1996Denver, , 1997Matsuda et al, 2010;Stengel and Tache, 2015).…”

Stress and the Gastrointestinal System

“…The abnormal increase of central CRF1 signaling could contribute to the pathogenesis of anxiety and depression as well as to IBS [ 11 , 80 , 161 ]. CRF2 receptors in the brain dampen and/or facilitate the proper recovery of the CRF1-initiated behavioral, endocrine, and visceral responses to stress [ 154 ] and have a primary role in the anorexic response to exogenous administration of CRF and Ucns [ 177 ]. CRFbinding protein (332-aa) isolated in different species functions as an endogenous antagonist by sequestrating CRF ligands, thus modulating the access of CRF and related peptides to CRF receptors [ 16 ].…”